TY - JOUR
T1 - In vivo killing of primary HIV-infected cells by peripheral-injected early memory–enriched anti-HIV duoCAR T cells
AU - Anthony-Gonda, Kim
AU - Ray, Alex
AU - Su, Hang
AU - Wang, Yuge
AU - Xiong, Ying
AU - Lee, Danica
AU - Block, Ariele
AU - Chilunda, Vanessa
AU - Weiselberg, Jessica
AU - Zemelko, Lily
AU - Wang, Yen Y.
AU - Kleinsorge-Block, Sarah
AU - Reese, Jane S.
AU - de Lima, Marcos
AU - Ochsenbauer, Christina
AU - Kappes, John C.
AU - Dimitrov, Dimiter S.
AU - Orentas, Rimas
AU - Deeks, Steven G.
AU - Rutishauser, Rachel L.
AU - Berman, Joan W.
AU - Goldstein, Harris
AU - Dropulić, Boro
N1 - Publisher Copyright:
© 2022, Anthony-Gonda et al.
PY - 2022/11/8
Y1 - 2022/11/8
N2 - HIV-specific chimeric antigen receptor–T cell (CAR T cell) therapies are candidates to functionally cure HIV infection in people with HIV (PWH) by eliminating reactivated HIV-infected cells derived from latently infected cells within the HIV reservoir. Paramount to translating such therapeutic candidates successfully into the clinic will require anti-HIV CAR T cells to localize to lymphoid tissues in the body and eliminate reactivated HIV-infected cells such as CD4+ T cells and monocytes/ macrophages. Here we show that i.v. injected anti-HIV duoCAR T cells, generated using a clinical-grade anti-HIV duoCAR lentiviral vector, localized to the site of active HIV infection in the spleen of humanized mice and eliminated HIV-infected PBMCs. CyTOF analysis of preinfusion duoCAR T cells revealed an early memory phenotype composed predominantly of CCR7+ stem cell–like/central memory T cells (TSCM/TCM) with expression of some effector-like molecules. In addition, we show that anti-HIV duoCAR T cells effectively sense and kill HIV-infected CD4+ T cells and monocytes/ macrophages. Furthermore, we demonstrate efficient genetic modification of T cells from PWH on suppressive ART into anti-HIV duoCAR T cells that subsequently kill autologous PBMCs superinfected with HIV. These studies support the safety and efficacy of anti-HIV duoCAR T cell therapy in our presently open phase I/IIa clinical trial (NCT04648046).
AB - HIV-specific chimeric antigen receptor–T cell (CAR T cell) therapies are candidates to functionally cure HIV infection in people with HIV (PWH) by eliminating reactivated HIV-infected cells derived from latently infected cells within the HIV reservoir. Paramount to translating such therapeutic candidates successfully into the clinic will require anti-HIV CAR T cells to localize to lymphoid tissues in the body and eliminate reactivated HIV-infected cells such as CD4+ T cells and monocytes/ macrophages. Here we show that i.v. injected anti-HIV duoCAR T cells, generated using a clinical-grade anti-HIV duoCAR lentiviral vector, localized to the site of active HIV infection in the spleen of humanized mice and eliminated HIV-infected PBMCs. CyTOF analysis of preinfusion duoCAR T cells revealed an early memory phenotype composed predominantly of CCR7+ stem cell–like/central memory T cells (TSCM/TCM) with expression of some effector-like molecules. In addition, we show that anti-HIV duoCAR T cells effectively sense and kill HIV-infected CD4+ T cells and monocytes/ macrophages. Furthermore, we demonstrate efficient genetic modification of T cells from PWH on suppressive ART into anti-HIV duoCAR T cells that subsequently kill autologous PBMCs superinfected with HIV. These studies support the safety and efficacy of anti-HIV duoCAR T cell therapy in our presently open phase I/IIa clinical trial (NCT04648046).
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U2 - 10.1172/jci.insight.161698
DO - 10.1172/jci.insight.161698
M3 - Article
C2 - 36345941
AN - SCOPUS:85141893576
SN - 2379-3708
VL - 7
JO - JCI Insight
JF - JCI Insight
IS - 21
M1 - e161698
ER -